Beta-Lactamase Repressor BlaI Modulates Staphylococcus aureus Cathelicidin Antimicrobial Peptide Resistance and Virulence.

BlaI is a repressor of BlaZ, the beta-lactamase responsible for penicillin resistance in Staphylococcus aureus. Through screening a transposon library in S. aureus Newman for susceptibility to cathelicidin antimicrobial peptide, we discovered BlaI as a novel cathelicidin resistance factor. Additionally, through integrational mutagenesis in S. aureus Newman and MRSA Sanger 252 strains, we confirmed the role of BlaI in resistance to human and murine cathelidicin and showed that it contributes to virulence in human whole blood and murine infection models. We further demonstrated that BlaI could be a target for innate immune-based antimicrobial therapies; by removing BlaI through subinhibitory concentrations of 6-aminopenicillanic acid, we were able to sensitize S. aureus to LL-37 killing

PHOTZIP: A Lossy FITS Image Compression Algorithm that Protects User-Defined Levels of Photometric Integrity

A lossy compression algorithm is presented for astronomical images that protects photometric integrity for detected point sources at a user-defined level of statistical tolerance. PHOTZIP works by modeling, smoothing, and then compressing the astronomical background behind self-detected point sources, while completely preserving values in and around those sources. The algorithm also guaranties a maximum absolute difference (in terms of $\sigma$) between each compressed and original background pixel, allowing users to control quality and lossiness. For present purposes, PHOTZIP has been tailored to FITS format and is freely available over the web. PHOTOZIP has been tested over a broad range of astronomical imagery and is in routine use by the Night Sky Live (NSL) project for compression of all-sky FITS images. Compression factors depend on source densities, but for the canonical NSL implementation, a PHOTZIP (and subsequently GZIP or BZIP2) compressed file is typically 20% of its uncompressed size.Comment: 10 pages, 3 figures. Accepted for publication in A

The Disk and Dark Halo Mass of the Barred Galaxy NGC 4123. I. Observations

The non-circular streaming motions in barred galaxies are sensitive to the mass of the bar and can be used to lift the degeneracy between disk and dark matter halo encountered when fitting axisymmetric rotation curves of disk galaxies. In this paper, we present photometric and kinematic observations of NGC 4123, a barred galaxy of modest size (V_rot = 130 km/sec, L = 0.7 L_*), which reveal strong non-circular motions. The bar has straight dust lanes and an inner Lindblad resonance. The disk of NGC 4123 has no sign of truncation out to 10 scale lengths, and star-forming regions are found well outside R_25. A Fabry-Perot H-alpha velocity field shows velocity jumps of >100 km/sec at the location of the dust lanes within the bar, indicating shocks in the gas flow. VLA observations yield the velocity field of the H I disk. Axisymmetric mass models yield good fits to the rotation curve outside the bar regionfor disk I-band M/L of 2.25 or less, and dark halos with either isothermal or power-law profiles can fit the data well. In a companion paper, we model the full 2-D velocity field, including non-circular motions, to determine the stellar M/L and the mass of the dark halo.Comment: accepted by ApJ, 16 pages, 9 figures (1 color), uses emulateapj.sty, onecolfloat.st

The properties of the Galactic bar implied by gas kinematics in the inner Milky Way

Longitude-velocity (l-V) diagrams of H I and CO gas in the inner Milky Way have long been known to be inconsistent with circular motion in an axisymmetric potential. Several lines of evidence suggest that the Galaxy is barred, and gas flow in a barred potential could be consistent with the observed ``forbidden'' velocities and other features in the data. We compare the H I observations to l-V diagrams synthesized from 2-D fluid dynamical simulations of gas flows in a family of barred potentials. The gas flow pattern is very sensitive to the parameters of the assumed potential, which allows us to discriminate among models. We present a model that reproduces the outer contour of the H I l-V diagram reasonably well; this model has a strong bar with a semimajor axis of 3.6 kpc, an axis ratio of approximately 3:1, an inner Lindblad resonance (ILR), and a pattern speed of 42 km/s/kpc, and matches the data best when viewed from 34\deg to the bar major axis. The behavior of the models, combined with the constraint that the shocks in the Milky Way bar should resemble those in external barred galaxies, leads us to conclude that wide ranges of parameter space are incompatible with the observations. In particular we suggest that the bar must be fairly strong, must have an ILR, and cannot be too end-on, with the bar major axis at 35\deg +/- 5\deg to the line of sight. The H I data exhibit larger forbidden velocities over a wider longitude range than are seen in molecular gas; this important difference is the reason our favored model differs so significantly from other recently proposed models.Comment: 23 pages, 14 figures, 1 table, uses emulateapj and psfig, 640 kb. Submitted to Ap

Mapping the Asymmetric Thick Disk I. A Search for Triaxiality

A significant asymmetry in the distribution of faint blue stars in the inner Galaxy, Quadrant 1 (l = 20 to 45 degrees) compared to Quadrant 4 was first reported by Larsen & Humphreys (1996). Parker et al (2003, 2004) greatly expanded the survey to determine its spatial extent and shape and the kinematics of the affected stars. This excess in the star counts was subsequently confirmed by Juric et al. (2008) using SDSS data. Possible explanations for the asymmetry include a merger remnant, a triaxial Thick Disk, and a possible interaction with the bar in the Disk. In this paper we describe our program of wide field photometry to map the asymmetry to fainter magnitudes and therefore larger distances. To search for the signature of triaxiality, we extended our survey to higher Galactic longitudes. We find no evidence for an excess of faint blue stars at l > 55 degrees including the faintest magnitude interval. The asymmetry and star count excess in Quadrant 1 is thus not due to a triaxial Thick Disk.Comment: 36 pages, 8 figures. Accepted by Astronomical Journa

Comparative effectiveness of dual-action versus single-action antidepressants for the treatment of depression in people living with HIV/AIDS

Background Depression is the most common psychiatric comorbidity among people living with HIV/AIDS (PLWHA). Little is known about the comparative effectiveness between different types of antidepressants used to treat depression in this population. We compared the effectiveness of dual-action and single-action antidepressants in PLWHA for achieving remission from depression. Methods We used data from the Centers for AIDS Research Network of Integrated Clinic Systems to identify 1175 new user dual-action or single-action antidepressant treatment episodes occurring from 2005 to 2014 for PLWHA diagnosed with depression. The primary outcome was remission from depression defined as a Patient Health Questionnaire-9 (PHQ-9) score <5. Mean difference in PHQ-9 depressive symptom severity was a secondary outcome. The main approach was an intent-to-treat (ITT) evaluation complemented with a per protocol (PP) sensitivity analysis. Generalized linear models were fitted to estimate treatment effects. Results In ITT analysis, 32% of the episodes ended in remission for both dual-action and single-action antidepressants. The odds ratio (OR) of remission was 1.02 (95%CI=0.63,1.67). In PP analysis, 40% of dual-action episodes ended in remission compared to 32% in single-action episodes. Dual-action episodes had 1.33 times the odds of remission (95%CI=0.55,3.21), however the result was not statistically significant. Non-significant differences were also observed for depressive symptom severity. Limitations Missing data was common but was addressed with inverse probability weights. Conclusions Results suggest that single-action and dual-action antidepressants are equally effective in PLWHA. Remission was uncommon highlighting the need to identify health service delivery strategies that aid HIV providers in achieving full remission of their patients’ depression

Physical Structure and Nature of Supernova Remnants in M101

Supernova remnant (SNR) candidates in the giant spiral galaxy M101 have been previously identified from ground-based H-alpha and [SII] images. We have used archival Hubble Space Telescope (HST) H-alpha and broad-band images as well as stellar photometry of 55 SNR candidates to examine their physical structure, interstellar environment, and underlying stellar population. We have also obtained high-dispersion echelle spectra to search for shocked high-velocity gas in 18 SNR candidates, and identified X-ray counterparts to SNR candidates using data from archival observations made by the Chandra X-ray Observatory. Twenty-one of these 55 SNR candidates studied have X-ray counterparts, although one of them is a known ultra-luminous X-ray source. The multi-wavelength information has been used to assess the nature of each SNR candidate. We find that within this limited sample, ~16% are likely remnants of Type Ia SNe and ~45% are remnants of core-collapse SNe. In addition, about ~36% are large candidates which we suggest are either superbubbles or OB/HII complexes. Existing radio observations are not sensitive enough to detect the non-thermal emission from these SNR candidates. Several radio sources are coincident with X-ray sources, but they are associated with either giant HII regions in M101 or background galaxies. The archival HST H-alpha images do not cover the entire galaxy and thus prevents a complete study of M101. Furthermore, the lack of HST [SII] images precludes searches for small SNR candidates which could not be identified by ground-based observations. Such high-resolution images are needed in order to obtain a complete census of SNRs in M101 for a comprehensive investigation of the distribution, population, and rates of SNe in this galaxy.Comment: 37 pages, 4 Tables, 7 Figures, accepted for publication in the Astronomical Journa

Surface enhanced raman scattering artificial nose for high dimensionality fingerprinting

Label-free surface-enhanced Raman spectroscopy (SERS) can interrogate systems by directly fingerprinting its components’ unique physicochemical properties. In complex biological systems however, this can yield highly overlapping spectra that hinder sample identification. Here, we present an artificial-nose inspired SERS fingerprinting approach where spectral data is obtained as a function of sensor surface chemical functionality. Supported by molecular dynamics modelling, we show that mildly selective self-assembled monolayers can influence the strength and configuration in which analytes interact with plasmonic surfaces, diversifying the resulting SERS fingerprints. Since each sensor generates a modulated signature, the implicit value of increasing the dimensionality of datasets is shown using cell lysates for all possible combinations of up to 9 fingerprints. Reliable improvements in mean discriminatory accuracy towards 100% is achieved with each additional surface functionality. This arrayed label-free platform illustrates the wide-ranging potential of high dimensionality artificial-nose based sensing systems for more reliable assessment of complex biological matrices